Is PITPNM3 p.Arg900= (c.2700C>T) pathogenic?

PITPNM3 p.Arg900= (c.2700C>T) is classified Conflicting classifications of pathogenicity in PITPNM3 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-03). Rare (popmax 0.118%, sas).

How common is PITPNM3 p.Arg900= (c.2700C>T) in the general population?

PITPNM3 p.Arg900= (c.2700C>T) is rare (popmax 0.118%, sas) (gnomAD).

PITPNM3 p.Arg900=

c.2700C>T · rs139901820 · VCV195534

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.118%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.82	GERP -1.9, phastCons 0.001
Overall
CADD	7.983	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.118% South Asian · 107/90,964 alleles

Filtering AF 0.0995% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0928%

Overall 0.025% 401/1,602,300 alleles · rare exomes 374/1,451,886 · genomes 27/150,414 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.118%	850
Middle Eastern	0.0495%	2,019
Remaining individualsnot grpmax-eligible	0.0337%	2,971
European (non-Finnish)	0.0223%	4,484
Admixed American	0.00835%	11,972
African / African-American	0.00269%	37,161

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PITPNM3
Protein: p.Arg900=
Coding: c.2700C>T
MANE Select: NM_031220
dbSNP: rs139901820
Type: single nucleotide variant
Location: chr17:6455563 (GRCh38)
Gene constraint: LOEUF 0.354 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.73 · 1 PDB

Full PITPNM3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PITPNM3 p.Arg900Cys Uncertain significance ★ same residue
PITPNM3 p.Arg900Ser Uncertain significance ★ same residue
PITPNM3 c.2306+6T>A Uncertain significance ★★ same type
PITPNM3 c.351+3A>C Uncertain significance ★★ same type
PITPNM3 c.351+5G>A Uncertain significance ★★ same type
PITPNM3 c.*2957G>A Uncertain significance ★★ same type
PITPNM3 c.*3446G>T Uncertain significance ★★ same type
PITPNM3 c.*3452C>G Uncertain significance ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/pitpnm3-p-arg900 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown